The program describes proposed research on the regulation of macromolecular and membrane changes in aging rats, mice, nematodes and slime mold, and on the significance of the changes to the phenomenon of aging. Morphological, functional and biosynthetic changes in mitochondria will be analyzed. A search for long-lived mutants of nematodes will be initiated. Investigations on cross-linking, turnover and ultrastructure of collagen as a function of age will be continued. The age-related changes that take place in mouse skin glycosaminoglycans will be defined and the role of anabolic hormones in the appearance of the changes explored. The factors controlling protein catabolism will be analyzed with respect to specific changes that may have to precede proteolysis.